This project examines the structure of several membrane proteins to determine how their conformations reflect their functional roles, and the means by which proteins fold in hydrophobic environments. It utilizes a number of spectroscopic techniques, including 13C and 1H-nuclear magnetic resonance (NMR) and circular dichroism (CD), to determine details of the molecular configuration and orientation of these molecules in membranes. The secondary structure of a number of membrane proteins, including the H ion-ATPase proteolipid, the erythrocyte anion transport protein (band III) NaKATPase, gramicidin, fd bacteriophage coat protein, and human fibronectin are examined to provide insight into the general folding patterns for membrane proteins and permit model building. The structural manifestations of physiological effectors such as substrates and inhibitors on these proteins are detected in difference spectra and provide information on their mechanism of action. Detailed structural studies on bacteriorhodopsin, band III and the ATPase proteolipid using 1H-and 13C-NMR will define the nature of the active site and the location and orientation of the N-, and C-termini with respect to the membrane surface. These spectroscopic studies are intended to provide high resolution information concerning the active site conformation, molecular orientation, changes with physiological effectors, and modes or protein folding in the hydrophobic environment of the membrane.